Adult injured axons can regenerate and functional recovery is achievable if appropriate biochemical and structural environments are present. While several in vivo studies have shown that neurotrophic factors (NF) can rescue neuronal cells, promote axonal growth and restore function after nerve injury, there is little clinical success using present delivery strategies. We have used a gene-activated matrix (GAM) to deliver a NF called fibroblast growth factor (FGF2) as condensed DNA in optic nerve injury and shown neuron survival over 100 days after injury. The protein is ineffective at this time point. We will now deliver other NF genes with and without targeting to neuronal cells to determine if increased selectivity of delivery of NFs enhances cell survival and nerve regeneration. The studies are designed to develop therapeutic DNA(s) that, when delivered after CNS injury, can promote sustained survival and regeneration. This approach of gene delivery may provide a high transfection rate, higher efficiency due to cellular selectivity and sustained levels of neurotrophic factors. PROPOSED COMMERCIAL APPLICATION: These studies will validate the use of Gene Activated Matrices (GAM) for promotion of survival and regeneration of nerve cells after injury. The commercial application wil provide a novel and long lasting targeting gene therapy to deliver therapeutic genes after CNS injury. The success of these experiments will benefit patients with hemi and paraplegia and other patients with CNS injury. At present, few treatment options are available for these patients.